We report that norepinephrine markedly increases excitability of neonatal rat optic nerves. To investigate the mechanisms of the norepinephrine-induced excitability increase, we studied isolated optic nerves from 42 neonatal (< three days old) and five adult (> three months old) Long-Evan's hooded rats. Norepinephrine (10-6, 10-5 and 10-4 M) rapidly and reversibly increased the amplitudes (mean ± S.D.: 3.5 ± 1.7%, 12.1 ± 2.8% and 35.6 ± 8.4%) of compound action potentials elicited by submaximal stimulation of neonatal optic nerves. The beta-1 adrenoceptor antagonist atenolol (10-5 M) blocked the norepinephrine-induced increase in excitability but the alpha antagonist phentolamine (10-5 M) did not. The beta agonist isoproterenol (10-5 and 10-4 M) increased response amplitudes (8.7 ± 4.1% and 25.8 ± 4.6%) but the alpha-1 agonist and methoxamine and alpha-2 agonist clonidine did not. The beta antagonist propranolol blocked the isoproterenol effect. Replacing Ca2+ with Mg2+ or adding 0.8 mM of Cd2+ reversibly blocked the norepinephrine effects. Extracellular K+ concentrations did not change in optic nerves during norepinephrine application. Blockade of K+ channels with apamin (10-6 M) or tetraethylammonium (10-3 M) did not prevent the excitatory effects of norepinephrine. Adult rat optic nerves were insensitive to both norepinephrine (10-4 M) and isoproterenol (10-4 M). Our results indicate that norepinephrine increases neonatal optic axonal excitability through Ca2+-dependent mechanisms. The data suggest that the adrenoceptors are situated on the axons, that the excitability changes are not due to changes in extracellular K+ concentration or K+ channels sensitive to apamin or tetraethylammonium. The sensitivity of rat optic nerves to norepinephrine declined with age. Axonal adrenoceptors may play a role in optic axonal development and injury.
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